Naylor P H, Oates K K, Coss M C, Erdos M R, Naylor C W, Goldstein A L
Department of Biochemistry and Molecular Biology, George Washington University, School of Medicine and Health Sciences, Washington, D.C. 20037.
Int J Immunopharmacol. 1992 Oct;14(7):1267-78. doi: 10.1016/0192-0561(92)90063-q.
Thymosin alpha 1 (T alpha 1) is a biologically active peptide, originally isolated from the thymus and currently undergoing clinical trials as an immunomodulator in cancer patients, in individuals with chronic active hepatitis, and as an immunoenhancer of vaccines in immunocompromised individuals. Absorption of rabbit antibody to thymosin alpha 1 with a synthetic C-14 fragment of T alpha 1 results in an antiserum with increased affinity for the amino terminal region of T alpha 1 and the precursor protein prothymosin alpha (ProT alpha). Using HPLC methodologies, the predominant form of immunoreactivity in serum and thymus was T alpha 1 not the precursor. Using this assay we detected a decline in mouse serum T alpha 1 following irradiation but not thymectomy, an observation consistent with the existence of an important radiation sensitive lymphoid source of serum T alpha 1. The secretion of authentic T alpha 1 but not the precursor into culture medium by thymic epithelial cells as well as in mitogen-stimulated peripheral blood lymphocytes was also demonstrated by HPLC/RIA. HPLC analysis by molecular weight sizing columns demonstrated that unlike thymic epithelial cells or peripheral blood lymphocytes, the immunoreactive T alpha 1 (IRT alpha 1) form in the supernatants from tumor cells such as MCF-7 breast carcinoma was of a lower molecular weight than authentic T alpha 1. These studies suggest that the authentic form of T alpha 1 is the major immunoreactive form in normal serum and that it is secreted by the medullary thymic epithelial cells as well as by peripheral blood lymphocytes. An additional immunoreactive form, secreted by tumor cells has also been identified and is the subject of future studies.
胸腺素α1（Tα1）是一种生物活性肽，最初从胸腺中分离出来，目前正在作为免疫调节剂用于癌症患者、慢性活动性肝炎患者的临床试验，以及作为免疫受损个体疫苗的免疫增强剂。用Tα1的合成C-14片段吸收兔抗胸腺素α1抗体，可产生对Tα1的氨基末端区域和前体蛋白前胸腺素α（ProTα）亲和力增加的抗血清。使用高效液相色谱法（HPLC），血清和胸腺中免疫反应性的主要形式是Tα1而非前体。使用该检测方法，我们检测到照射后小鼠血清Tα1下降，但胸腺切除后未下降，这一观察结果与血清Tα1存在重要的辐射敏感淋巴来源一致。高效液相色谱/放射免疫分析（HPLC/RIA）也证明了胸腺上皮细胞以及丝裂原刺激的外周血淋巴细胞将 authentic Tα1而非前体分泌到培养基中。通过分子量大小分离柱进行的HPLC分析表明，与胸腺上皮细胞或外周血淋巴细胞不同，肿瘤细胞（如MCF-7乳腺癌细胞）上清液中的免疫反应性Tα1（IRTα1）形式的分子量低于 authentic Tα1。这些研究表明， authentic Tα1的形式是正常血清中主要的免疫反应形式，它由胸腺髓质上皮细胞以及外周血淋巴细胞分泌。还鉴定出了肿瘤细胞分泌的另一种免疫反应形式，这是未来研究的主题。
